tbuckley/cabot-search huggingface dataset:
Lower vs Higher Oxygen Saturation Targets and Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest—Reply
Authors: Stephen Bernard, Janet Bray
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Targeting type 2 immunity and the future of food allergy treatment
Authors: M. Cecilia Berin
Journal: The Journal of Experimental Medicine (2023)

IgE-mediated food allergy affects 6–8% of the population in the United States. Type 2 immune responses are central to the pathogenesis of food allergy, but type 2 CD4+ T cell responses have been found to be heterogeneous in food allergy suggesting a division of labor between Tfh13 and peTH2 cells in promotion of IgE class switching, modulation of intestinal barrier function, and regulation of mast cell expansion. Oral immunotherapy for the treatment of food allergy incompletely targets subsets of type 2 immunity in a transient manner, but new therapeutics targeting different levels of type 2 immunity are in current or planned trials for food allergy. These new treatments and the basis for their use are the focus of this review.
Enzymatic Self‐Assembly of Adamantane‐Peptide Conjugate for Combating <i>Staphylococcus aureus</i> Infection
Authors: Wenjun Zhan, Ge Gao, Zhiyu Liu, Xiaoyang Liu, Lingling Xu, Manli Wang, Hai‐Dong Xu, Runqun Tang, Jingyuan Cao, Xianbao Sun, Gaolin Liang
Journal: Advanced Healthcare Materials (2023)

Abstract Staphylococcus aureus ( S. aureus ) remains a leading cause of bacterial infections. However, eradication of S. aureus infections with common antibiotics is increasingly difficult due to outbreaks of drug resistance. Therefore, new antibiotic classes and antibacterial strategies are urgently in demand. Herein, it is shown that an adamantane‐peptide conjugate, upon dephosphorylation by alkaline phosphatase (ALP) constitutively expressed on S. aureus , generates fibrous assemblies in situ to combat S. aureus infection. By attaching adamantane to a phosphorylated tetrapeptide Nap‐Phe‐Phe‐Lys‐Tyr(H 2 PO 3 )‐OH, the rationally designed adamantane‐peptide conjugate Nap‐Phe‐Phe‐Lys(Ada)‐Tyr(H 2 PO 3 )‐OH (Nap‐FYp‐Ada) is obtained. Upon bacterial ALP activation, Nap‐FYp‐Ada is dephosphorylated and self‐assembles into nanofibers on the surface of S. aureus . As revealed by cell assays, the assemblies of adamantane‐peptide conjugates interact with cell lipid membrane and thereby disrupt membrane integrity to kill S. aureus . Animal experiments further demonstrate the excellent potential of Nap‐FYp‐Ada in the treatment of S. aureus infection in vivo. This work provides an alternative approach to design antimicrobial agents.
Tissue iron distribution in patients with anemia of inflammation: Results of a pilot study
Authors: Lukas Lanser, Michaela Plaikner, Andrea Schroll, Francesco Robert Burkert, Stefanie Seiwald, Josia Fauser, Verena Petzer, Rosa Bellmann‐Weiler, Gernot Fritsche, Ivan Tancevski, Christina Duftner, Andreas Pircher, Andreas Seeber, Heinz Zoller, Christian Kremser, Benjamin Henninger, Günter Weiss
Journal: American Journal of Hematology (2023)

Anemia of inflammation (AI) is frequently present in subjects with inflammatory disorders, primarily caused by inflammation-driven iron retention in macrophages. So far, only limited data on qualitative and quantitative estimates of tissue iron retention in AI patients exist. We performed a prospective cohort study analyzing splenic, hepatic, pancreatic, and cardiac iron content with MRI-based R2*-relaxometry in AI patients, including subjects with concomitant true iron deficiency (AI+IDA) hospitalized between 05/2020-01/2022. Control groups were individuals without inflammation. Spleen R2* values in AI patients with ferritin ≤200 μg/L (AI+IDA) were comparable with those found in controls. In AI patients with ferritin >200 μg/L, spleen (47.6 s-1 vs. 19.3 s-1 , p < .001) and pancreatic R2* values (32.5 s-1 vs. 24.9 s-1 , p = .011) were significantly higher compared with controls, while liver and heart R2*-values did not differ. Higher spleen R2* values were associated with higher ferritin, hepcidin, CRP, and IL-6 concentrations. Spleen R2* values normalized in AI patients after recovery (23.6 s-1 vs. 47.6 s-1 , p = .008), while no changes were found in patients with baseline AI+IDA. This is the first study investigating tissue iron distribution in patients with inflammatory anemia and AI with concomitant true iron deficiency. The results support the findings in animal models demonstrating iron retention in macrophages, which are primarily accumulating in the spleen under inflammatory conditions. MRI-related iron measurement may help to better characterize actual iron needs and to define better biomarker thresholds in the diagnosis of true ID in patients with AI. It may qualify as a useful diagnostic method to estimate the need for iron supplementation and to guide therapy.
Effect of exercise therapy versus surgery on mechanical symptoms in young patients with a meniscal tear: a secondary analysis of the DREAM trial
Authors: Camma Damsted, Jonas Bloch Thorlund, Per Hölmich, Martin Lind, Claus Varnum, Martin Dalgaard Villumsen, Mogens Strange Hansen, Søren T Skou
Journal: British Journal of Sports Medicine (2023)

Objective To compare the effect of early surgery versus exercise and education on mechanical symptoms and other patient-reported outcomes in patients aged 18–40 years with a meniscal tear and self-reported mechanical knee symptoms. Methods In a randomised controlled trial, 121 patients aged 18–40 years with a MRI-verified meniscal tear were randomised to surgery or 12-week supervised exercise and education. For this study, 63 patients (33 and 30 patients in the surgery and in the exercise group, respectively) reporting baseline mechanical symptoms were included. The main outcome was self-reported mechanical symptoms (yes/no) at 3, 6 and 12 months assessed using a single item from the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes were KOOS 4 and the 5 KOOS-subscales and the Western Ontario Meniscal Evaluation Tool (WOMET). Results In total, 55/63 patients completed the 12-month follow-up. At 12 months, 9/26 (35%) in the surgery group and 20/29 (69%) in the exercise group reported mechanical symptoms. The risk difference and relative risk at any time point was 28.7% (95% CI 8.6% to 48.8%) and 1.83 (95% CI 0.98 to 2.70) of reporting mechanical symptoms in the exercise group compared with the surgery group. We did not detect any between-group differences in the secondary outcomes. Conclusion The results from this secondary analysis suggest that early surgery is more effective than exercise and education for relieving self-reported mechanical knee symptoms, but not for improving pain, function and quality of life in young patients with a meniscal tear and mechanical symptoms. Trial registration number NCT02995551 .
Health Equity Measures and Hospital Rankings
Authors: Ge Bai, Kosali Simon, Peter Cram
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Lower vs Higher Oxygen Saturation Targets and Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest
Authors: Wolfgang A. Wetsch, Bernd W. Böttiger
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Enzyme‐Triggered <scp>l</scp>‐<i>α</i>/<scp>d</scp>‐Peptide Hydrogels as a Long‐Acting Injectable Platform for Systemic Delivery of HIV/AIDS Drugs
Authors: Sophie M. Coulter, Sreekanth Pentlavalli, Lalitkumar K. Vora, Yuming An, Emily R. Cross, Ke Peng, Kate McAulay, Ralf Schweins, Ryan F. Donnelly, Helen O. McCarthy, Garry Laverty
Journal: Advanced Healthcare Materials (2023)

Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organization. Patient adherence to complicated dosage regimens remains a key barrier. There is a need for convenient long-acting formulations that deliver drugs over sustained periods. This paper presents an alternative platform, an injectable in situ forming hydrogel implant to deliver a model antiretroviral drug (zidovudine [AZT]) over 28 days. The formulation is a self-assembling ultrashort d or l-α peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), covalently conjugated to zidovudine via an ester linkage. Rheological analysis demonstrates phosphatase enzyme instructed self-assembly, with hydrogels forming within minutes. Small angle neutron scattering data suggest hydrogels form narrow radius (≈2 nm), large length fibers closely fitting the flexible cylinder elliptical model. d-Peptides are particularly promising for long-acting delivery, displaying protease resistance for 28 days. Drug release, via hydrolysis of the ester linkage, progress under physiological conditions (37 °C, pH 7.4, H
Prominent 68Ga-FAPI Uptake in Renal Parenchyma Caused by Immunoglobulin G4–Related Nephropathy
Authors: Hongzhe Zhang, Qingqing Pan, Yaping Luo
Journal: Clinical Nuclear Medicine (2023)

A 57-year-old man presented with a dry cough and renal insufficiency. Serum immunoglobulin G4 (IgG4) level was markedly elevated, and IgG4-related disease was clinically considered. 18 F-FDG PET/CT revealed mild uptake in salivary glands and also moderately increased activity in renal parenchyma and prostate. 68 Ga-FAPI PET/CT detected prominent and evenly distributed 68 Ga-FAPI uptake in the kidney, and the pancreas, salivary gland, and prostate also showed intense activity, consistent with IgG4-related disease involving the kidney, pancreas, salivary gland, and prostate.
Use of Leukotriene-Receptor Antagonists During Pregnancy and Risk of Neuropsychiatric Events in Offspring
Authors: Hui-Ju Tsai, Chi-Shin Wu, Yen-Chen Chang, Tsung-Chieh Yao
Journal: JAMA Network Open (2023)

This cohort study examines the association of the use of leukotriene-receptor antagonists during pregnancy with the risk of neuropsychiatric events in offspring.
Advances in the Treatment of Gastroenteropancreatic Neuroendocrine Carcinomas: Are we Moving Forward?
Authors: Rocio Garcia-Carbonero, Beatriz Anton-Pascual, Andrea Modrego, Maria del Carmen Riesco-Martinez, Alberto Lens-Pardo, Carlos Carretero-Puche, Beatriz Rubio-Cuesta, Beatriz Soldevilla
Journal: Endocrine Reviews (2023)

Abstract Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic disease. Current standard of care still follows the treatment paradigm of small cell lung cancer, a far more common G3 neuroendocrine neoplasm, although emerging molecular and clinical data increasingly question this approach. In this article, we will briefly summarize epidemiology and prognosis of gastroenteropancreatic neuroendocrine carcinomas to emphasize the very low incidence, aggressive nature, and orphan status of this tumor entity. We will also discuss the current pathological classification and its limitations, as well as recent data on their differential biological background compared with small cell lung cancer, and its potential implications for patients care. Then, we will review the standard of care of systemic therapy, basically focused on platinum-based cytotoxic chemotherapy, including some recent randomized trials providing evidence regarding efficacy of irinotecan vs etoposide platinum doublets. Finally, we will present a comprehensive overview of novel therapeutic strategies in current clinical development, including recently reported data on immunotherapy, tumor-agnostic therapies (microsatellite instability, high tumor mutational burden, NTRK and RET gene fusions, BRAF or KRAS inhibitors), and additional treatment strategies targeting other tumor vulnerabilities (ie, Notch pathway, novel targets for radioligand therapy), and provide some insights regarding unmet needs and future perspectives to improve patient's care and prognosis.
Intestinal cell type-specific communication networks underlie homeostasis and response to Western diet
Authors: Yu-Chen Wang, Yang Cao, Calvin Pan, Zhiqiang Zhou, Lili Yang, Aldons J. Lusis
Journal: The Journal of Experimental Medicine (2023)

The small intestine plays a key role in immunity and mediates inflammatory responses to high fat diets. We have used single-cell RNA-sequencing (scRNA-seq) and statistical modeling to examine gaps in our understanding of the dynamic properties of intestinal cells and underlying cellular mechanisms. Our scRNA-seq and flow cytometry studies of different layers of intestinal cells revealed new cell subsets and modeled developmental trajectories of intestinal intraepithelial lymphocytes, lamina propria lymphocytes, conventional dendritic cells, and enterocytes. As compared to chow-fed mice, a high-fat high-sucrose (HFHS) “Western” diet resulted in the accumulation of specific immune cell populations and marked changes to enterocytes nutrient absorption function. Utilizing ligand–receptor analysis, we profiled high-resolution intestine interaction networks across all immune cell and epithelial structural cell types in mice fed chow or HFHS diets. These results revealed novel interactions and communication hubs among intestinal cells, and their potential roles in local as well as systemic inflammation.
A decade of liver organoids: Advances in disease modeling
Authors: Yue Liu, Jian-Ying Sheng, Chun-Fang Yang, Junjun Ding, Yun-Shen Chan
Journal: Clinical and Molecular Hepatology (2023)

Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.
An anti-mesothelin targeting antibody drug conjugate induces pyroptosis and ignites antitumor immunity in mouse models of cancer
Authors: Nicole L Wittwer, Alexander H Staudacher, Vasilios Liapis, Pina Cardarelli, Harriet Warren, Michael P Brown
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Emerging evidence suggests that the mechanism of chemotherapy-induced cell death may influence the antitumor immune response in patients with cancer. Unlike immunologically silent apoptosis, pyroptosis is a lytic and inflammatory form of programmed cell death characterized by pore formation in the cell membrane and release of proinflammatory factors. Gasdermin E (GSDME) has recently gained attention after cleavage of GSDME by certain chemotherapeutics has been shown to elicit pyroptosis. This study investigated the immunomodulatory effects of a mesothelin-targeting antibody drug conjugate (ADC) in mouse models of breast and colon cancer. Methods The antitumor effects of the ADC were studied in EMT6 breast cancer and CT26 colon cancer syngeneic mouse models. The immunomodulatory effects of the ADC were assessed by analysis of tumor-infiltrating immune cells using flow cytometry. ADC mechanism of action was evaluated by morphology, biological assays, ADC-mediated cleavage of key effector proteins, and CRISPR/Cas9-mediated knockout (KO). Finally, the antitumor effect of ADC and Fms-like tyrosine kinase-3 ligand (Flt3L) combination therapy was evaluated in tumors expressing GSDME as well as in GSDME-silenced tumors. Results The data demonstrated that the ADC controlled tumor growth and stimulated anticancer immune responses. Investigation of the mechanism of action revealed that tubulysin, the cytotoxic payload of the ADC, induced cleavage of GSDME and elicited pyroptotic cell death in GSDME-expressing cells. Using GSDME KO, we showed that GSDME expression is critical for the effectiveness of the ADC as a monotherapy. Combining the ADC with Flt3L, a cytokine that expands dendritic cells in both lymphoid and non-lymphoid tissues, restored control of GSDME KO tumors. Conclusions Together, these results show for the first time that tubulysin and a tubulysin containing ADC can elicit pyroptosis, and that this fiery cell death is critical for antitumor immunity and therapeutic response.
Covid-19: US studies show racial and ethnic disparities in long covid
Authors: Janice Hopkins Tanne
Journal: BMJ (2023)

Black and Hispanic Americans are more likely than white Americans to have symptoms of long covid and some people who had covid early in the epidemic may have long covid but not be diagnosed as such because of coding changes, show studies funded by the National Institutes of Health. 1 -3 Long covid was defined by the Centers for Disease Control and Prevention in December 2022, and includes general symptoms as well as respiratory, cardiovascular, neurological, digestive, and other symptoms. 44 CDC.Long covid or post-covid conditions.16 December 2022.
High response rates and transition to transplant after novel targeted and cellular therapies in adults with relapsed/refractory acute lymphoblastic leukemia with <scp>Philadelphia‐like</scp> fusions
Authors: Ibrahim Aldoss, Michelle Afkhami, Dongyun Yang, Zhaohui Gu, Sally Mokhtari, Shilpa Shahani, Hoda Pourhassan, Vaibhav Agrawal, Paul Koller, Shukaib Arslan, Vanina Tomasian, Monzr M. Al Malki, Andrew Artz, Amandeep Salhotra, Haris Ali, Ahmed Aribi, Karamjeet S. Sandhu, Brian Ball, Salman Otoukesh, Idoroenyi Amanam, Pamela S. Becker, Forrest M. Stewart, Peter Curtin, Eileen Smith, Milhan Telatar, Anthony S. Stein, Guido Marcucci, Stephen J. Forman, Ryotaro Nakamura, Vinod Pullarkat
Journal: American Journal of Hematology (2023)

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is associated with a poor response to standard chemotherapy. However, outcomes with novel antibody and cellular therapies in relapsed/refractory (r/r) Ph-like ALL are largely unknown. We conducted a single-center retrospective analysis of adult patients (n = 96) with r/r B-ALL and fusions associated with Ph-like who received novel salvage therapies. Patients were treated with 149 individual novel regimens (blinatumomab = 83, inotuzumab ozogamicin [InO] = 36, and CD19CAR T cells = 30). The median age at first novel salvage therapy was 36 years (range; 18-71). Ph-like fusions were IGH::CRLF2 (n = 48), P2RY8::CRLF2 (n = 26), JAK2 (n = 9), ABL-class (n = 8), EPOR::IGH (n = 4) and ETV6::NTRK2 (n = 1). CD19CAR T cells were administered later in the course of therapy compared to blinatumomab and InO (p < .001) and more frequently in recipients who relapsed after allogeneic hematopoietic cell transplantation (alloHCT) (p = .002). Blinatumomab was administered at an older age compared to InO and CAR T-cells (p = .004). The complete remission (CR)/CR with incomplete hematologic recovery (CRi) rates were 63%, 72%, and 90% following blinatumomab, InO and CD19CAR, respectively, among which 50%, 50%, and 44% of responders underwent consolidation with alloHCT, respectively. In multivariable analysis, the type of novel therapy (p = .044) and pretreatment marrow blasts (p = .006) predicted the CR/CRi rate, while the Ph-like fusion subtype (p = .016), pretreatment marrow blasts (p = .022) and post-response consolidation with alloHCT (p < .001) influenced event-free survival. In conclusion, novel therapies are effective in inducing high remission rates in patients with r/r Ph-like ALL and successfully transitioning the responders to alloHCT.
Protamine-mediated efficient transcellular and transmucosal delivery of proteins
Authors: Jiamin Wu, Natalie Jones, Nojoud A.L. Fayez, Po-Han Chao, Angeline Wu, Daniele Ribeiro de Araujo, Elham Rouhollahi, Analisa Jia, Shyh-Dar Li
Journal: Journal of Controlled Release (2023)